New research reveals how PFAS chemicals disrupt human liver cells, causing fat buildup, immune interference, and cancer-related changes.
They’re called ‘forever chemicals’ for a reason. Per- and polyfluoroalkyl substances (PFAS), used in everyday products like nonstick pans, food wrappers, and waterproof fabrics, are nearly impossible to break down once released into the environment.
Over time, they build up in the human body, and scientists have long suspected they contribute to serious health issues.
Now, new research from the Keck School of Medicine of USC reveals exactly how these pollutants harm liver cells, offering a clearer picture of the dangers lurking beneath the surface.
Why the liver takes the hit
The liver is the body’s main detox organ, constantly filtering blood and processing harmful substances.
But this protective role makes it highly vulnerable to PFAS, which sneak into the bloodstream through drinking water, packaged foods, and consumer goods.
Unlike natural toxins that the liver can break down, PFAS remain intact, accumulating in tissues and interfering with normal cellular functions.
For years, researchers have seen a link between PFAS exposure and liver disease, as well as higher risks of cancer. What they couldn’t explain was the ‘how.’
That’s where the new study comes in – offering the most detailed look yet at the cellular consequences of PFAS exposure.
Inside the lab: Recreating the human liver
Instead of relying on animal testing, the USC team turned to an advanced 3D model known as a spheroid.
Built from real human liver cells donated by men and women, these miniature organs replicate the structure and behaviour of a living liver. This setup gave scientists an unprecedented view of how PFAS disrupt the organ at the smallest scale.
Four PFAS compounds commonly detected in human blood were tested individually:
- PFOA
- PFHxS
- PFOS
- PFNA
For seven days, the liver spheroids were exposed to these chemicals before being broken down into single cells for genetic and metabolic analysis.
Different chemicals, different damage
The results revealed that not all PFAS behave the same way – but none are harmless.
- PFOA and PFHxS: Both led to fat accumulation in liver cells, but through different biological processes. One increased fat production, while the other slowed fat release, ultimately leading to the same outcome – cells overloaded with fat.
- PFOS and PFNA: These two chemicals were linked to changes in cell activity associated with cancer. PFNA in particular raised red flags, with more than 60% of affected liver cells showing disruptions in pathways tied to inflammation, oxidative stress, and DNA repair.
Across all four chemicals, the team observed interference with immune processes and breakdowns in communication between liver cells, which may explain why long-term exposure is linked to chronic liver problems.
Surprising sex-specific differences
Another striking finding was that liver cells from male and female donors responded differently. PFOA had a stronger impact on female cells, while PFOS caused more damage in male cells.
These sex-specific patterns suggest that treatments for PFAS-related liver damage may need to be personalised.
Implications for health and treatment
By pinpointing how PFAS interfere with liver cells, researchers are paving the way for new medical approaches.
Some FDA-approved drugs that regulate fat processing in the liver could be repurposed to address PFAS-related conditions, potentially accelerating treatment options.
But prevention remains the most urgent priority. Because PFAS are so persistent, reducing exposure is the most effective way to protect liver health.
This means filtering drinking water, limiting the use of nonstick cookware, and being mindful of consumer products that may contain PFAS.
The next chapter in PFAS research
Researchers are now analysing the combined effects of multiple PFAS on liver cells – a scenario that more closely mirrors real-world exposure.
As science uncovers more about these chemicals, the evidence is mounting: PFAS are not just persistent in the environment, but also persistent in the body.
And among the organs they affect, liver cells appear to be on the front line of damage.
